Endocrinol. Japon. 1989, 36(1), 167-173 NOTE Plasma Aldosterone Level in a Female Case of Pseudohyperaldosteronism (Liddle's Syndrome) KAZUHISA TAKEUCHI, KEISHI ABE*, MAKITO SATO, MINORU YASUJIMA, KEN OMATA, OSAMU MURAKAMI AND KAORU YOSHINAGA Second Department of Internal Medicine, and *Department of Clinical Biology and Hormonal Regulation, Tohoku University, School of Medicine, 1-1 Seiryo-cho, Sendai 980, Japan Abstract A 22-yr-old female suffering from hypertension, hypokalemic alkalosis and suppressed plasma renin activity was studied. The plasma aldosterone con- centration (PAC) ranged between subnormal and normal levels while the other adrenal mineralocorticoids were normal. Examinations through computed. tomography and ultrasonography showed no abnormal findings. For dif- erential diagnosis, dexamethasone, spironolactone and triamterene were ad- ministered. Triamterene alone corrected the abnormalities in this case, and the therapeutic effect was further enhanced by sodium restriction. There- fore, the present case is strongly suggested to be one of Liddle's syndrome, which is characterized by a primary defect in renal tubular sodium handling and can be corrected with triamterene. However, the patient in our study is different from the first reported case in which aldosterone secretion was estimated to be low. Analysis of the changes in PAC has shown that PAC is parallel with the level of plasma progesterone in accordance with the rhythm of the menstrual cycle and, in the follicular phase, PAC is rather low. It is concluded that the patient was suffering from Liddle's syndrome, and it is assumed that PAC is not always subnormal and, as same as in normal females, PAC may change in accordance with the rhythm of the menstrual cycle in a female case of Liddle's syndrome. Pseudohyperaldosteronism is characteriz- either aldosterone or other endogenous ed by hypertension, hypokalemia and hy- mineralocortico id excess (Biglieri, 1981; poreninemia, suggesting a diagnosis of Sebastian et al., 1982). This state is brought primary aldosteronism. However, pseudo- about by several factors, including the hyperaldosteronism is not associated with administration of synthetic mineralocorti- coids, and the ingestion of substances Received September 22, 1988 causing mineralocorticoid-like activity, as Address correspondence to KAZUHISA TAKE- UCHI, M. D., Second Department of Internal well as Liddle's syndrome. Liddle's syn- Medicine, Tohoku University, School of Medi- drome is markedly different from the other cine, 1-1 Seiryo-cho, Sendai 980, Japan conditions, because its synptoms are not Endocrinol. Japon. 168 TAKEUCHI et al. February 1989 due to the renal action of mineralocorticoid was again confirmed. In spite of the but to a primary defect in renal sodium- administration of a calcium antagonist , potassium handling in renal distal tubules. nifedipine 60mg/day, and a potassium The present case was considered to be a supplement of K+ 24mEq/day, the abnor- case of Liddle's syndrome, although the malities persisted and she was referred to plasma aldosterone concentration (PAC) was our department for a thorough examination. not consistantly subnormal. We evaluated It was determined that she had no history the change in PAC in relation to the men- of excessive licorice ingestion, steroid hor- strual cycle and demonstrated a close rela- mone abuse or use of contraceptives. tionship between them. A physical examination showed the patient to be a phenotypically normal female, 160cm in height, weighing 50kg , Case Report and having no abnormal skin pigmentation . She had normal secondary sexual character- A 22-yr-old female suffering from hy- istics and a regular menstrual cycle. Her pertension and hypokalemia was admitted menarche had occurred at age 12. Blood to our department. She had been complain- pressure ranged between 200/120 and 150/ ing of recurrent headaches and general 100mmHg. Her chest X-ray was normal . muscular weakness for several years. An However, electrocardiography revealed left aunt (on her mother's side of the family) ventricular hypertrophy, and fundoscopic had died suddenly of an unkown etiology examination revealed mild ateriolar thicken- at the age of 35, and an uncle , on the ing. Her serum sodium level was found to same side, had died of kidney disease with be 144mEq/L and serum potassium 2.6 edema at age 5. mEq/L (normal value; 3.4-4.2mEq/L). Eight years before admission to our Arterial blood gas analysis showed the department, a school examination had dis- following: PH, 7.47; standard bicarbonate, closed that the patient was suffering from 30.8mmol/L; pCO2, 44.1mmHg; pO2, 88.0 high blood pressure (180/110mmHg) . At mmHg; and base excess, + 7.2mEq/L. that time, she was referred to the depart- Blood urea nitrogen was found to be 12 ment of pediatrics of a general hospital . and creatinine 1.1mg/dl. A complete Tests showed that she had hypertension blood count, urinalysis, and measurements (blood pressure ranged between 190/130 of serum concentrations of calcium, phos- and 170/100mmHg), hypokalemia (serum phorus, magnesium, albumin, globulin, potassium 2.8mEq/L). Plasma renin activity glucose, uric acid, lactic dehydrogenase, (PRA) was low and the plasma aldosterone glutamic-oxaloacetic transaminase and cho- concentration (PAC) was in the high-normal lesterol were done. All were found to be range. A tentative diagnosis of primary within normal limits. Creatinine clearance aldosteronism was made, and 75mg/day of was 73ml/min and para-amino hippuric spironolactone was administered. However, acid clearance 468ml/min. The findings her headaches persisted and the other ab- of travenous pyelography were normal. normal findings remained. After a few Urinary catecholamines, 17-ketosteroids (17- months, she refused to take the medication KS) and 17-hydroxycorticosteroids (17- and terminated her hospital visits. A few OHCS) were normal. PRA was undetec- months before admission to our department, table (<2.5ng/ml/6hr; normal value: 5- she visited a physician due to a common 30ng/ml/6hr), PAC was low within normal cold. At that time, her blood pressure was limits (2.4 ng/dl; normal value: 2-12ng/dl). found to be 180/100mmHg and hypokalemia Adrenal scintigram with 131I-adosterol (6ƒÀ- Vol. 36, No. 1 PLASMA ALDOTERONE LEVELS IN LIDDLE'S SYNDROME 169 iodomethyl-19-nor- cholest-5 (10)-en-3ƒÀ-ol, 80mEq/day. Daiichi Radioisotopes Laboratories Ltd., Blood pressure was measured with a standard sphygmomanometer at 0600h in recumbency Tokyo) showed diffuse accumulation of 131I every day. Plasma ACTH, aldosterone, cortisol, on bilateral adrenals and the uptake of 131I progesterone, corticosterone, deoxycorticosterone almost disappeared with the administration (DOC) and 18-hydroxy-deoxycorticosterone (18- of dexamethasone. Examinations through OH-DOC) were measured by radioimmunoassay echosonography and computed tomo- using commercially available kits (Dinabot Co., graphy showed normal findings in the Tokyo). PRA was measured by radioimmuno- abdomen. assay of angiotensin I as previously reported These data were not consistent with the (Abe et al., 1973). 19-hydroxyandrostenedione was measured by Dr. Sekihara of Tokyo Uni- usual findings in primary aldosteronism. versity. Therefore, further diagnostic examinations, including administration of dexamethasone, spironolactone and triamterene were carried Results out. Baseline Condition (Fig. 1) Methods High blood pressure persisted during this period. Serum potassium was 2.6 All examinations were carried out during 4 mEq/L. Urinary excretion of potassium months' hospitalization. The patient recieved a was above 50mEq/day, suggesting the salt restricted diet containing less than 5g NaCl kidney's inability to conserve potassium. (Na+ 85mEq)/day for a full month; for the PRA was undetectable during the furosemide remainder of her stay, she recieved a regular test. PAC was normal (5.8ng/dl) and diet containing 12g NaCl (Na+ 200mEq)/day constant during the furosemide test. Corti- and K+ 80 mEq/day. During hospitalization, 60 mg nifidipine and 50mg/day atenolol had to be costerone, DOC and 18-OH-DOC were all administered to prevent a hypertensive crisis, within normal limits. Urinary 17-OHCS because high blood pressure and complaints of and 17-KS excretions were normal. The headache persisted following admission. In a basal plasma cortisol level (8.0ƒÊg/dl) was furosemide test, blood samples were collected normal (normal value: 5-16 ƒÊg/dl) and to measure PRA and PAC after the patient had showed a normal response to the rapid stood upright for one and two hours, respec- ACTH test, because the basal plasma tively, following the intravenous injection of furosemide 60mg. A rapid ACTH test was cortisol level was increased to 17.3, 17.4 performed by intravenous injection of 250ƒÊg of and 24.5ƒÊg/dl at 30, 60 or 90min after α1-24ACTH(Cortrosyn: Daiichi Co., Tokyo), the injection of ACTH, respectively. In the as well as a dexamethasone, supression test by dexamethasone (Dx.) suppression test, the means of the oral administration of either 1 or basal plasma cortisol (5.4ƒÊg/dl) was de- 8mg of dexamethasone. Four studies on meta- creased to an undetectable level either by bolic balance were carried out to examine changes in blood pressure and renal electrolyte Dx. 1mg or Dx. 8mg, indicating a normal excretion in response to: 1) inhibition of adrenal response, whereas PAC showed a very weak biosynthesis by dexamethasone 2mg/day for 2 response to both a stimulatory and an in- weeks; 2) administration of triamterene 100 and hibotory procedure. In the rapid ACTH 200mg/day for 3 weeks; 3) administration of test, the basal PAC (8.0ng/dl) was not triamterene 200mg/day and salt restriction (Nat changed significantly at 30 min (8.5ng/dl), 85mEq/day) and, 4) blockade of mineralocorti- coid hormone receptors using 150 and 300mg/ 60min (9.3ng/dl) or 90min (10.1ng/dl) day spironolactone for 2 weeks. During these after the injection of ACTH, and in the Dx. periods dietary potassium was kept at around suppression test, the basal PAC (9.6ng/dl) Endocrinol. Japon. 170 TAKEUCHI et al.